US3122547A - 2, 4, 7-triamino-6-pteridine carboxamides - Google Patents
2, 4, 7-triamino-6-pteridine carboxamides Download PDFInfo
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- US3122547A US3122547A US241524A US24152462A US3122547A US 3122547 A US3122547 A US 3122547A US 241524 A US241524 A US 241524A US 24152462 A US24152462 A US 24152462A US 3122547 A US3122547 A US 3122547A
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- Prior art keywords
- triamino
- pteridine
- carboxamides
- nitrosopyrimidine
- acetamide
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- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D475/00—Heterocyclic compounds containing pteridine ring systems
- C07D475/06—Heterocyclic compounds containing pteridine ring systems with a nitrogen atom directly attached in position 4
- C07D475/08—Heterocyclic compounds containing pteridine ring systems with a nitrogen atom directly attached in position 4 with a nitrogen atom directly attached in position 2
Definitions
- this invention is concerned with 2,4- 7-triamino-6-substituted-pteridines and in particular with those compounds of this class which have the following general formula:
- n is an integer ranging from 4 to 6;
- m is an integer ranging from 2 to 3 and R is a straight chain or branched alkyl group having from 1 to 4 carbon atoms.
- a preferred synthesis for the novel compounds of this invention involves the reaction, in an anhydrous neutral polar solvent in the presence of a basic catalyst, of 2,4,6- triamino-S-nitrosopyrimidine (II) with a 2-cyano-r -(substituted)-acetamide or with a N-cyanoacetylpolymethyleneimine ('III).
- reaction mixture is heated at temperatures of above 50 C. and below 200 C. and preferably at the boiling temperature of the selected inert solvent. This reaction is run for about 20 minutes to 2 hours and proceeds as follows:
- Suitable inert solvents for this reaction include methanol, ethanol, 2-ethoxyethanol (Cellosolve), butanol, 2- methoxyethanol, methoxy and ethoxy propanols, dimethyl formamide, diethyl formamide and dimethyl acetamide.
- Basic catalysts suitable for promoting the above-outlined reaction include the alkali rnetals, their alkoxides and their alkoxy .alkoxides. Preferred among these are sodium metal, sodium methoxide and sodium a-ethoxy ethoxide.
- Example 1 To a solution of 1.0 g. of sodium in 500 ml. of dry 2 ethoxyethanol was added 6.16 g. of 2,4,6-triamino-5-nitrosopyrimidine, and the mixture was stirred mechanically and brought to boiling point. This was followed by the addition of 7.37 g. of 2-cyano-N-(3-isopropoxypropyl) acetamide. The mixture was then boiled under reflux for 1 hour during which time the red solution turned dark brown. The solution thus obtained was concentrated almost to dryness, and the residue was treated with ml. of Water when a brown material was deposited, M.P. 265270 C.
- Example 2 2,4,7 triamino N (2 ethoxyethyl) 6 pteridine carboxamide is prepared from 6.9 g. of 2-cyano-N-(2- ethoxyethyl) acetamide and 6.16 g. of 2,4,6-triamino-5- nitrosopyrimidine, as described in Example 1.
- Example 3 2,4,7 triamino N (2 methoxyethyl) 6 pteridinecarboxamide is prepared from 6.44 g. of 2-cyano-N-(2- methoxyethyl) acetamide and 6.16 g. of 2,4,6-triamino- S-nitrosopyrimidine, as described in Example 1.
- Example 4 2,4,7 triamino N (3 butoxypropyl) 6 pteridinecarboxamide is prepared from 7.28 g. of 2-cyano-N-(3- butoxypropyl) acetamide and 6.16 g. of 2,4,6-triamino-5- nitrosopyrimidine, according to essentially the same procedure of Example 1.
- Example 5 To a stirred solution of 1.03 g. of sodium metal in 500 ml. of absolute Cellosolve was added 6.16 g. of 2,4,6- triamino-S-nitrosopyrimidine. The mixture was heated under reflux and 9.5 g. of N-cyanoacetyl hexamethyleneimine was added. Heating under reflux was continued for 2 hours, during which time some solid material was deposited out of solution. The reaction mixture was filtered and the filtrate was concentrated to dryness on the rotary evaporator. The residue was then triturated with 100 ml. of water to give a yellow solid. Crystallization of the product from Cellos-olve afforded 1-(2,4,7-tri amino 6 pteridylcarbonyl) hexamethyleneimine; M.P. 305-6" C.
- Example 7 By reaction of 6.16 g. of 2,4,6-triamino-S-nitrosopyrimidine with 6.28 g. of 1-cyanoacetylpyrrolidine, 1-(2,4,7- triarnino-6-pteridylcarbonyl)pyrrolidine is obtained, as in Example 6.
- the compounds of this invention are useful in experimental pharmacology. Those compounds where Z represents generally exhibit diuretic and antiviral activities. Those pounds.
- the present invention also includes the process of bringing the compounds thereof into a form suitable for therapeutic administration by associating them with liquid or solid pharmaceutical carriers.
- Z is selected from the group consisting of:
- n is an integer ranging from 4 to 6;
- m is an integer ranging from 2 to 3 and R is an alkyl group having from 1 to 4 carbon atoms.
Description
United States Patent Ofi" 3,122,547 Patented Feb. 25, 1954 This invention relates to novel pteridine compounds having valuable pharmacological properties. 1
More specifically, this invention is concerned with 2,4- 7-triamino-6-substituted-pteridines and in particular with those compounds of this class which have the following general formula:
wherein Z represents:
where n is an integer ranging from 4 to 6; or
where m is an integer ranging from 2 to 3 and R is a straight chain or branched alkyl group having from 1 to 4 carbon atoms.
A preferred synthesis for the novel compounds of this invention involves the reaction, in an anhydrous neutral polar solvent in the presence of a basic catalyst, of 2,4,6- triamino-S-nitrosopyrimidine (II) with a 2-cyano-r -(substituted)-acetamide or with a N-cyanoacetylpolymethyleneimine ('III).
The reaction mixture is heated at temperatures of above 50 C. and below 200 C. and preferably at the boiling temperature of the selected inert solvent. This reaction is run for about 20 minutes to 2 hours and proceeds as follows:
where Z is as hereinabove stated.
Suitable inert solvents for this reaction include methanol, ethanol, 2-ethoxyethanol (Cellosolve), butanol, 2- methoxyethanol, methoxy and ethoxy propanols, dimethyl formamide, diethyl formamide and dimethyl acetamide.
Basic catalysts suitable for promoting the above-outlined reaction include the alkali rnetals, their alkoxides and their alkoxy .alkoxides. Preferred among these are sodium metal, sodium methoxide and sodium a-ethoxy ethoxide.
The following examples illustrate the best mode of carrying out the invention.
Example 1 To a solution of 1.0 g. of sodium in 500 ml. of dry 2 ethoxyethanol was added 6.16 g. of 2,4,6-triamino-5-nitrosopyrimidine, and the mixture was stirred mechanically and brought to boiling point. This was followed by the addition of 7.37 g. of 2-cyano-N-(3-isopropoxypropyl) acetamide. The mixture was then boiled under reflux for 1 hour during which time the red solution turned dark brown. The solution thus obtained was concentrated almost to dryness, and the residue was treated with ml. of Water when a brown material was deposited, M.P. 265270 C. Fractional crystallization from ethanol, followed by recrystallization from the same solvent gave 2, 4,7 triamino N (3 isopropoxypropyl) 6 pteridinecarboxamide, as yellow hygroscopic crystals, M.P. 278 C.
Analysis.Calculated: C=48.74, H=6.29, N=34.98. Found: C=48.43, H=6.67, N=34.39.
Example 2 2,4,7 triamino N (2 ethoxyethyl) 6 pteridine carboxamide is prepared from 6.9 g. of 2-cyano-N-(2- ethoxyethyl) acetamide and 6.16 g. of 2,4,6-triamino-5- nitrosopyrimidine, as described in Example 1.
Example 3 2,4,7 triamino N (2 methoxyethyl) 6 pteridinecarboxamide is prepared from 6.44 g. of 2-cyano-N-(2- methoxyethyl) acetamide and 6.16 g. of 2,4,6-triamino- S-nitrosopyrimidine, as described in Example 1.
Example 4 2,4,7 triamino N (3 butoxypropyl) 6 pteridinecarboxamide is prepared from 7.28 g. of 2-cyano-N-(3- butoxypropyl) acetamide and 6.16 g. of 2,4,6-triamino-5- nitrosopyrimidine, according to essentially the same procedure of Example 1.
Example 5 To a stirred solution of 1.03 g. of sodium metal in 500 ml. of absolute Cellosolve was added 6.16 g. of 2,4,6- triamino-S-nitrosopyrimidine. The mixture was heated under reflux and 9.5 g. of N-cyanoacetyl hexamethyleneimine was added. Heating under reflux was continued for 2 hours, during which time some solid material was deposited out of solution. The reaction mixture was filtered and the filtrate was concentrated to dryness on the rotary evaporator. The residue was then triturated with 100 ml. of water to give a yellow solid. Crystallization of the product from Cellos-olve afforded 1-(2,4,7-tri amino 6 pteridylcarbonyl) hexamethyleneimine; M.P. 305-6" C.
Analysis.-Calculated: 6:51.64, H:6.00, N:37.07. Found: C=51.27, H=6.32, N=36.43.
Example 6 To a solution of 1.0 g. of sodium in 400 ml. of dry 2- ethoxyethanol was added 6.16 g. of 2,4,6-triamino-5-nitrosopyrimidine, and the solution was stirred and brought to boiling point. This was followed by the addition of 6.84 g. of l-cyanoacetylpiperidine and the mixture was boiled under reflux for 20 minutes. The mixture was cooled and the red precipitate which was present was removed by filtration and discarded. Concentration of the filtrate afiorded a light brown material, wt.=4.6 g.; M.P. 300310 (decomposition). Several recrystallizations from aqueous 2-ethoxyethanol yielded yellow crystals of l-(2,4,7 triamino 6 pteridylcarbonyl)piperidine, MP. 305-307 (decomposition).
Analysis.Calculated: (3:49.99, H=5.59, N=38.87. Found: C=49.73, H=6.01, N=38.67.
Example 7 By reaction of 6.16 g. of 2,4,6-triamino-S-nitrosopyrimidine with 6.28 g. of 1-cyanoacetylpyrrolidine, 1-(2,4,7- triarnino-6-pteridylcarbonyl)pyrrolidine is obtained, as in Example 6.
The compounds of this invention are useful in experimental pharmacology. Those compounds where Z represents generally exhibit diuretic and antiviral activities. Those pounds.
The present invention also includes the process of bringing the compounds thereof into a form suitable for therapeutic administration by associating them with liquid or solid pharmaceutical carriers.
Various changes and modifications of this invention can be made by those skilled in the art to which it relates and to the extent that such variations incorporate the spirit of the invention, they are included in the scope of the claims.
wherein Z is selected from the group consisting of:
A -N (CH2)n Where n is an integer ranging from 4 to 6; and
i -N(CHz)mOR Where m is an integer ranging from 2 to 3 and R is an alkyl group having from 1 to 4 carbon atoms.
2. 2,4,7 triamino N (3 isopropoxypropyl) 6- pteridinecarboxamide.
3. 1-(2,4,7-triamino 6 pteridylcarbonyl) hexamethyleneimine.
4. 1-(2,4,7-triamino-6-pteridylcarbonyl)-piperidine.
References Cited in the file of this patent Osdene et al.: J. Chem. Soc., London (1955), pages 2036-38.
Claims (1)
1. A COMPOUND HAVING THE FORMULA:
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US241524A US3122547A (en) | 1962-12-03 | 1962-12-03 | 2, 4, 7-triamino-6-pteridine carboxamides |
| BE634346A BE634346A (en) | 1962-07-02 | 1963-07-01 | New pteridine compounds |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US241524A US3122547A (en) | 1962-12-03 | 1962-12-03 | 2, 4, 7-triamino-6-pteridine carboxamides |
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| Publication Number | Publication Date |
|---|---|
| US3122547A true US3122547A (en) | 1964-02-25 |
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| Application Number | Title | Priority Date | Filing Date |
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| US241524A Expired - Lifetime US3122547A (en) | 1962-07-02 | 1962-12-03 | 2, 4, 7-triamino-6-pteridine carboxamides |
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| US (1) | US3122547A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090017716A1 (en) * | 2007-07-11 | 2009-01-15 | Michael Marzetta | Construction system |
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- 1962-12-03 US US241524A patent/US3122547A/en not_active Expired - Lifetime
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| None * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090017716A1 (en) * | 2007-07-11 | 2009-01-15 | Michael Marzetta | Construction system |
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